Frontline evaluation: Atezolizumab-bevacizumab versus lenvatinib for BCLC stage B hepatocellular carcinoma exceeding the up-to-seven criteria.

INTRODUCTION: This study aimed to evaluate the efficacy and safety of atezolizumab combined with bevacizumab (Atez/Bev) compared to lenvatinib (LEN) as first-line systemic therapy for patients with Barcelona Clinic Liver Cancer (BCLC) stage B hepatocellular carcinoma (HCC) exceeding the up-to-seven criteria threshold, who are typically unsuitable for transarterial chemoembolization (TACE). METHODS: A retrospective analysis was conducted on 49 consecutive patients with HCC treated at Tokyo Metropolitan Komagome Hospital between May 2018 and October 2023. The patients were divided into two groups: the Atez/Bev group (21 patients) and the LEN group (28 patients). Eligibility criteria included Child-Pugh A classification, no prior systemic therapy, and ineligibility for resection, ablation, or transplantation. Treatment outcomes were assessed through periodic imaging and laboratory tests, evaluating OS, PFS, ORR, and disease control rate (DCR). RESULTS: Both groups demonstrated comparable baseline characteristics, with a median follow-up of 15.4 months. No significant difference was observed in OS between the Atez/Bev and LEN groups (median OS: 19.80 vs. 22.20 months, p = 0.763). The median PFS was 10.23 months for Atez/Bev and 7.20 months for LEN (p = 0.343). There were no statistically significant differences in ORR or DCR between the two groups. Common adverse events included elevated AST and ALT levels, with no significant difference in the overall rate of adverse events between the groups. CONCLUSIONS: Atez/Bev and LEN demonstrated comparable efficacy and safety as first-line systemic treatments for patients with BCLC stage B HCC exceeding the up-to-seven criteria. Both therapeutic options are viable for this population, though further large-scale prospective studies are required to confirm these findings.

Prevalence of undiagnosed stage B heart failure among emergency department patients.

INTRODUCTION: Heart failure (HF) is associated with significant morbidity, mortality, and health care costs. Stage B HF is defined as structural heart disease prior to developing symptomatic HF. If identified early in the disease process, preventative measures may be implemented to slow disease progression to Stage C (symptomatic) or Stage D (refractory) HF. Previous research has focused on outpatient screening for HF in the primary care setting; however, there are limited data on Stage B HF screening in the Emergency Department (ED) setting. The objective of this study was to determine the prevalence of undiagnosed Stage B HF among those with cardiovascular risk factors in the ED setting and identify which risk factors were associated with a greater risk of having Stage B HF. METHODS: A prospective, observational study was performed in a single, urban academic ED from 07/2023 to 05/2024. Inclusion criteria were age ≥ 45 years with hypertension, diabetes, obesity, coronary heart disease, previous cardiotoxic chemotherapy, or family history of HF. Exclusion criteria included signs or symptoms of HF, known history of HF, valvular disease, current atrial fibrillation, or primary language other than English. A focused cardiac ultrasound was performed and interpreted by ultrasound-fellowship trained emergency physicians. Sonographers assessed systolic function as ejection fraction <50 % using visual assessment in at least two different views. Sonographers assessed diastolic dysfunction as an E/A ratio < 0.8, or if ≥2 of the following were present: septal e' < 7 cm/s or lateral e' < 10 cm/s, E/e' ratio > 14, or left atrial volume > 34 mL/m2. Descriptive statistics were performed, followed by comparative analyses and regression modeling. RESULTS: 209 participants were included in the study, with a mean age of 60 years and 51.7 % women. Of these, 125 (59.8 %) had undiagnosed Stage B HF, with 13 (10.4 %) having systolic dysfunction and 112 (89.6 %) having isolated diastolic dysfunction. Among those with isolated diastolic dysfunction, 44 (39.3 %) were grade I, 66 (58.9 %) were grade II, and 2 (1.8 %) were grade III. Predictors of undiagnosed Stage B HF included age (odds ratio 1.06; 95 % CI 1.02 to 1.10) and BMI (odds ratio 1.06; 95 % CI 1.01 to 1.10). CONCLUSION: A large majority of ED patients with cardiovascular risk factors had undiagnosed Stage B HF. Age and obesity were associated with a higher risk of Stage B HF. This provides an opportunity for early identification and intervention for patients with undiagnosed Stage B HF to reduce progression to more severe HF.

Circulating sphingolipids and relationship to cardiac remodelling before and following a low-energy diet in asymptomatic Type 2 Diabetes.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is a heterogenous multi-system syndrome with limited efficacious treatment options. The prevalence of Type 2 diabetes (T2D) continues to rise and predisposes patients to HFpEF, and HFpEF remains one of the biggest challenges in cardiovascular medicine today. Novel therapeutic targets are required to meet this important clinical need. Deep phenotyping studies including -OMIC analyses can provide important pathogenic information to aid the identification of such targets. The aims of this study were to determine; 1) the impact of a low-energy diet on plasma sphingolipid/ceramide profiles in people with T2D compared to healthy controls and, 2) if the change in sphingolipid/ceramide profile is associated with reverse cardiovascular remodelling. METHODS: Post-hoc analysis of a randomised controlled trial (NCT02590822) including adults with T2D with no cardiovascular disease who completed a 12-week low-energy (∼810 kcal/day) meal-replacement plan (MRP) and matched healthy controls (HC). Echocardiography, cardiac MRI and a fasting blood for lipidomics were undertaken pre/post-intervention. Candidate biomarkers were identified from case-control comparison (fold change > 1.5 and statistical significance p < 0.05) and their response to the MRP reported. Association between change in biomarkers and change indices of cardiac remodelling were explored. RESULTS: Twenty-four people with T2D (15 males, age 51.1 ± 5.7 years), and 25 HC (15 male, 48.3 ± 6.6 years) were included. Subjects with T2D had increased left ventricular (LV) mass:volume ratio (0.84 ± 0.13 vs. 0.70 ± 0.08, p < 0.001), increased systolic function but impaired diastolic function compared to HC. Twelve long-chain polyunsaturated sphingolipids, including four ceramides, were downregulated in subjects with T2D at baseline. Three sphingomyelin species and all ceramides were inversely associated with LV mass:volume. There was a significant increase in all species and shift towards HC following the MRP, however, none of these changes were associated with reverse cardiac remodelling. CONCLUSION: The lack of association between change in sphingolipids/ceramides and reverse cardiac remodelling following the MRP casts doubt on a causative role of sphingolipids/ceramides in the progression of heart failure in T2D. TRIAL REGISTRATION: NCT02590822.

Biomarkers for Heart Failure Prediction and Prevention.

Heart failure (HF) is a global pandemic affecting over 64 million people worldwide. Its prevalence is on an upward trajectory, with associated increasing healthcare expenditure. Organizations including the American College of Cardiology (ACC) and the American Heart Association (AHA) have identified HF prevention as an important focus. Recently, the ACC/AHA/Heart Failure Society of America (HFSA) Guidelines on heart failure were updated with a new Class IIa, Level of Evidence B recommendation for biomarker-based screening in patients at risk of developing heart failure. In this review, we evaluate the studies that have assessed the various roles and contributions of biomarkers in the prediction and prevention of heart failure. We examined studies that have utilized biomarkers to detect cardiac dysfunction or abnormality for HF risk prediction and screening before patients develop clinical signs and symptoms of HF. We also included studies with biomarkers on prognostication and risk prediction over and above existing HF risk prediction models and studies that address the utility of changes in biomarkers over time for HF risk. We discuss studies of biomarkers to guide management and assess the efficacy of prevention strategies and multi-biomarker and multimodality approaches to improve risk prediction.

IMbrave150: Efficacy and Safety of Atezolizumab plus Bevacizumab versus Sorafenib in Patients with Barcelona Clinic Liver Cancer Stage B Unresectable Hepatocellular Carcinoma: An Exploratory Analysis of the Phase III Study.

Introduction: The phase III IMbrave150 study established atezolizumab + bevacizumab as standard of care in patients with unresectable hepatocellular carcinoma (HCC). This exploratory analysis reports efficacy and safety results in patients with baseline Barcelona Clinic Liver Cancer (BCLC) stage B disease. Methods: Patients with systemic treatment-naive unresectable HCC and Child-Pugh class A liver function were randomized 2:1 to receive 1,200 mg of atezolizumab plus 15 mg/kg of bevacizumab or 400 mg of sorafenib. Co-primary endpoints were overall survival (OS) and progression-free survival (PFS) per independent review facility (IRF)-assessed Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1 in the BCLC stage B subgroup. Patients in this analysis had BCLC stage B disease at baseline per electronic case report form. Secondary efficacy endpoints included the objective response rate (ORR) and change in the sum of longest diameters (SLD) of target lesions from baseline per IRF RECIST 1.1 and modified RECIST (mRECIST) for HCC. Results: Of 501 enrolled patients, 74 (15%) had BCLC stage B disease at baseline (atezolizumab + bevacizumab, n = 49; sorafenib, n = 24). For this group, median follow-up was 19.7 months. A trend toward improved OS and PFS per IRF RECIST 1.1 was observed with atezolizumab + bevacizumab versus sorafenib (OS: hazard ratio [HR]: 0.63; 95% confidence interval [CI]: 0.29, 1.34; PFS: HR: 0.64; 95% CI: 0.36, 1.12). ORRs per IRF RECIST 1.1 and HCC mRECIST were 43% and 50% with atezolizumab + bevacizumab and 26% and 30% with sorafenib, respectively. Percentage change in SLD of target lesions from baseline per IRF RECIST 1.1 and HCC mRECIST showed durable responses with atezolizumab + bevacizumab treatment. Safety data were consistent with known profiles of atezolizumab and bevacizumab, as seen in the overall study population. Discussion/Conclusion: Efficacy benefits were observed with atezolizumab + bevacizumab in patients with baseline BCLC stage B disease, consistent with the intention-to-treat population.

Survival Prediction After Transarterial Chemoembolization for Hepatocellular Carcinoma: a Deep Multitask Survival Analysis Approach.

The accurate prediction of postoperative survival time of patients with Barcelona Clinic Liver Cancer (BCLC) stage B hepatocellular carcinoma (HCC) is important for postoperative health care. Survival analysis is a common method used to predict the occurrence time of events of interest in the medical field. At present, the mainstream survival analysis models, such as the Cox proportional risk model, should make strict assumptions about the potential random process to solve the censored data, thus potentially limiting their application in clinical practice. In this paper, we propose a novel deep multitask survival model (DMSM) to analyze HCC survival data. Specifically, DMSM transforms the traditional survival time prediction problem of patients with HCC into a survival probability prediction problem at multiple time points and applies entropy regularization and ranking loss to optimize a multitask neural network. Compared with the traditional methods of deleting censored data and strong hypothesis, DMSM makes full use of all the information in the censored data but does not need to make any assumption. In addition, we identify the risk factors affecting the prognosis of patients with HCC and visualize the importance of ranking these factors. On the basis of the analysis of a real dataset of patients with BCLC stage B HCC, experimental results on three different validation datasets show that the DMSM achieves competitive performance with concordance index of 0.779, 0.727, and 0.780 and integrated Brier score (IBS) of 0.172, 0.138, and 0.135, respectively. Our DMSM has a comparatively small standard deviation (0.002, 0.002, and 0.003) for IBS of bootstrapping 100 times. The DMSM we proposed can be utilized as an effective survival analysis model and provide an important means for the accurate prediction of postoperative survival time of patients with BCLC stage B HCC.

A Novel Standardized Method for Aiding to Determine Left Atrial Enlargement on Lateral Thoracic Radiographs in Dogs.

BACKGROUND: Left atrial enlargement indicates severe cardiac disease. Although the gold standard for determining left atrial size is echocardiography, many veterinary practices lack the necessary equipment and expertise. Therefore, thoracic radiography is often used to differentiate cardiogenic pulmonary edema from primary respiratory diseases and to facilitate distinguishing dogs with stage B1 and B2 mitral valve degeneration. METHODS: The goal was to test a new standardized method for identifying radiographic left atrial enlargement. On a lateral radiograph, a straight line was drawn from the dorsal border of the tracheal bifurcation to the crossing point of the dorsal border of the caudal vena cava and the most cranial crus of the diaphragm. If a part of the left atrium extended this line dorsally, it was considered enlarged. Echocardiographic left atrial to aortic ratio (LA:Ao) was used as a reference. Thirty-nine observers with various levels of experience evaluated 90 radiographs, first subjectively, then applying the new method. RESULTS: The new method moderately correlated with LA:Ao (r = 0.56-0.66) in all groups. The diagnostic accuracy (72-74%) of the subjective assessment and the new method showed no difference. CONCLUSIONS: Though the new method was not superior to subjective assessment, it may facilitate learning and subjective interpretation.

The aMAP Score is an Independent Risk Factor for Intermediate-stage Hepatocellular Carcinoma: A Large Retrospective Cohort Study.

Background: A less effective nomogram for patients with intermediate-stage hepatocellular carcinoma (HCC) to predict overall survival (OS) is available. This study aimed to investigate the role of age-male-albumin-bilirubin-platelet (aMAP) scores in the prognosis of patients with intermediate-stage HCC and develop an aMAP score-based nomogram to predict OS. Methods: Data on newly diagnosed intermediate-stage patients with HCC at Sun Yat-sen University Cancer Center between January 2007 and May 2012 were retrospectively collected. Independent risk factors affecting prognosis were selected by multivariate analyses. The optimal cut-off value for the aMAP score was determined using X-tile. The survival prognostic models were presented by the nomogram. Results: For the 875 patients with intermediate-stage HCC included, the median OS was 22.2 months (95% CI 19.6-25.1). Patients were classified into three groups by X-tile plots (aMAP score < 49.42; 49.42 ≤ aMAP score < 56; aMAP score ≥ 56). Alpha-fetoprotein, lactate dehydrogenase, aMAP score, diameter of main tumor, number of intrahepatic lesions, and treatment regimen were independent risk factors for prognosis. A predicted model was constructed with a C-index of 0.70 (95% CI: 0.68-0.72) in the training goup, and its 1-, 3-, and 5-year area under the receiver operating curve were: 0.75, 0.73, and 0.72. The validation group of the C-index is 0.82. Calibration graphs showed good consistency between the actual and predicted survival rates. The decision curve analysis suggested the clinical utility of the model, which may help clinicians guide clinical decision-making. Conclusion: The aMAP score was an independent risk factor for intermediate-stage HCC. The aMAP score-based nomogram has good discrimination, calibration, and clinical utility.

Living donor liver transplantation for Barcelona clinic liver cancer (BCLC) intermediate-stage hepatocellular carcinoma.

Background: Barcelona clinic liver cancer (BCLC) stage B (intermediate stage) hepatocellular carcinoma (HCC) is highly heterogeneous; thus, identifying the most effective treatment for individual patients represents a significant clinical challenge. However, transarterial chemoembolization (TACE) is the only recommended treatment option. Therefore, we aimed to investigate the patient characteristics and outcomes of living donor liver transplantation (LDLT) for BCLC stage B HCC. Methods: A total of 516 patients with BCLC stage B HCC who underwent LDLT (n=104) or did not undergo LDLT (non-LDLT; n=412) between 2004 to 2018 were analyzed by propensity score matching (PSM; 1:4) analysis. Factors influencing overall survival (OS) and recurrence were analyzed using Cox's proportional hazards models. Results: Patients treated with LDLT achieved better OS than the non-LDLT group, including liver- and non-liver related survival (all P<0.001). Multivariate Cox regression analysis showed age >60 years (P=0.006), a neutrophil-lymphocyte ratio (NLR) >4 (P=0.016) and >3 locoregional therapies (LRT) before LDLT (P<0.001) were independent risk factors for HCC recurrence. In addition, age >60 years (P<0.001) and >3 LRT before LDLT (P=0.001) were independent risk factors for OS. Using a combination of age, NLR, and LRT before liver transplantation (LT), the patients can be divided into low-risk (none of risk), intermediate-risk (one of risk), and high risk (more than two of risk) groups. There were significant differences in the cumulative HCC recurrence (P<0.001) and mortality (P<0.001) rates among the three groups. Conclusions: LDLT may represent a valuable therapeutic option for selected patients with BCLC stage B HCC.

Reclassification of Pre-Heart Failure Stages Using Cardiac Biomarkers: The ARIC Study.

BACKGROUND: The recent heart failure (HF) guideline recommends the inclusion of cardiac biomarkers in defining Stage B HF. OBJECTIVES: The authors evaluated the impact of incorporating cardiac biomarkers to reclassify HF in 5,324 participants (mean age: 75.8 years) without prevalent HF enrolled in the ARIC (Atherosclerosis Risk In Communities) study and assessed prognosis of Stage B using cardiac biomarkers. METHODS: Using N-terminal pro-B-type natriuretic peptide (<125 pg/mL or ≥125 pg/mL), high-sensitivity troponin T (<14 ng/L or ≥14 ng/L), and abnormal cardiac structure/function by echocardiography, individuals were classified as Stage Anew and Stage Bnew HF, respectively. Stage Bnew was further evaluated as elevated biomarker only, abnormal echocardiogram only, and abnormalities in both (echo + biomarker). The authors assessed risk for incident HF and all-cause death using Cox regression. RESULTS: Overall, 4,326 (81.3%) individuals were classified as Stage Bnew with 1,123 (21.1%) meeting criteria for elevated biomarkers only. Compared with Stage Anew, Stage Bnew was associated with increased risk for incident HF (HR: 3.70 [95% CI: 2.58-5.30]) and death (HR: 1.94 [95% CI: 1.53-2.46]). Stage Bbiomarkers only and Stage Becho only were associated with increased HF risk, whereas Stage Bbiomarkers only was also associated with increased death. Stage Becho+biomarker had the highest risk for HF (HR: 6.34 [95% CI: 4.37-9.19]) and death (HR: 2.53 [95% CI: 1.98-3.23]). CONCLUSIONS: Incorporating biomarkers based on the new HF guideline reclassified approximately 1 in 5 older adults without prevalent HF to Stage B. The routine measurement of biomarkers can help to identify individuals at higher HF risk who may benefit most from HF prevention efforts.

Prognostic Impact of a Novel Albumin-Platelet Index as Selection Criterion for Hepatic Resection in Intermediate Stage Hepatocellular Carcinoma.

BACKGROUND/AIM: Hepatic resection for Barcelona Clinic Liver Cancer (BCLC) stage B (intermediate-stage) hepatocellular carcinoma (HCC) is not recommended by BCLC treatment algorithms. We sought to develop a new prognostic model for determining appropriate treatment strategies in patients with intermediate-stage HCC. PATIENTS AND METHODS: This single-center retrospective study included patients who underwent hepatic resection for HCC between 2000 and 2018. A total of 498 patients were classified according to the BCLC staging system (0, n=116; A, n=319; B, n=63). The predictive impact for surgical outcomes was evaluated using receiver operating characteristic (ROC) curves. Based on a survival outcome probability formula, a new predictive model was established. RESULTS: The preoperative albumin level and platelet count were the strongest diagnostic values in patients with intermediate-stage HCC (areas under the ROC curves, AUCs: 0.710 and 0.676, respectively). Logistic regression analysis provided the albumin-platelet index [API; 156.2×albumin (g/dl)+platelet count (×109/l)] was defined as a new prognostic model for the probability of poor survival. The optimal cutoff value (781.2; AUC 0.755) divided patients with BCLC-B into B1 (>781.2, n=27) and B2 (≤781.2, n=36) categories. Patients in substage B2 had a significantly worse prognosis than patients in other stages (p<0.0001), whereas there was no difference in prognosis between patients in substage B1 and those in other stages. CONCLUSION: The API stratifies prognosis in patients with intermediate-stage HCC. For subgroup B1, hepatic resection can be considered a radical treatment, even for intermediate-stage HCC.

Impact of skeletal muscle volume on patients with BCLC stage-B hepatocellular carcinoma undergoing sorafenib therapy.

AIM: Skeletal muscle volume has been reported to be an important factor that determines overall survival (OS) and post-progression survival (PPS) in patients with hepatocellular carcinoma (HCC). However, the impact of skeletal muscle volume on HCC with Barcelona Clinic Liver Cancer (BCLC) stage B (BCLC-B) remains unclear. We conducted sub-analyses of a previous study on BCLC-B and compared our findings with data on HCC with BCLC stage C (BCLC-C). METHODS: We retrospectively enrolled 356 patients with HCC (BCLC-B, n = 78; and BCLC-C, n = 278) undergoing sorafenib therapy. Prognostic factors were analyzed using various parameters, including skeletal muscle volume. Muscle volume (MV) depletion was designated as less than the median value of the skeletal muscle index for each gender (cutoff value: 45.0 cm2 /m2 for male and 38.0 cm2 /m2 for female participants). RESULTS: Both OS and PPS showed no significant differences in patients with non-MV depletion and those with MV depletion in the BCLC-B group (Median OS [MST] 19.3 vs. 13.5 months [p = 0.348]; median PPS 9.7 vs. 10.8 months [p = 0.578]). In the BCLC-C group, patients with non-MV depletion had a significantly longer OS and PPS compared to patients with MV depletion (MST 12.4 vs. 9.0 months [p = 0.001] and median PPS 7.9 vs. 5.4 months [p = 0.002]). Multivariate analysis revealed that MV depletion was an independent prognostic factor of OS and PPS in the BCLC-C group but not in the BCLC-B group. CONCLUSIONS: Skeletal muscle volume showed little impact on the clinical outcomes of patients with BCLC-B undergoing sorafenib therapy.

Prevalence and prognosis of frailty in older patients with stage B heart failure with preserved ejection fraction.

AIMS: Frailty in older patients with stage B heart failure with preserved ejection fraction (HFpEF) has not been fully explored. We evaluated the prevalence and prognostic significance of frailty in older patients diagnosed with stage B HFpEF. METHODS: Our prospective cohort study included inpatients aged ≥65 years who were followed up for 3 years. Stage B HFpEF was defined as cardiac structural or functional abnormalities with a left ventricular ejection fraction (LVEF) ≥ 50% without signs or symptoms. Frailty was assessed using the Fried phenotype. The primary outcome was 3-year all-cause mortality or readmission. RESULTS: Overall, 520 older inpatients diagnosed with stage B HFpEF [mean ± standard deviation age: 75.5 ± 6.25 years, male: 222 (42.7%)] were included in the study. Of these, 145 (27.9%) were frail. Frail patients were older (78.5 ± 6.23 vs. 74.3 ± 6.22 years, P < 0.001), with a lower body mass index (24.6 ± 3.60 vs. 25.7 ± 3.27 kg/m2 , P = 0.001), higher level of N-terminal pro-B-type natriuretic peptide [279 (interquartile range: 112.4, 596) vs. 140 (67.1, 266) pg/mL, P < 0.001], longer timed up-and-go test result (19.9 ± 9.71 vs. 13.3 ± 5.08 s, P < 0.001), and poorer performance in the short physical performance battery (4.1 ± 3.26 vs. 8.2 ± 2.62, P < 0.001), basic activities of daily living (BADL, 4.7 ± 1.71 vs. 5.7 ± 0.57, P < 0.001), and instrumental activities of daily living (IADL, 4.4 ± 2.73 vs. 7.4 ± 1.33, P < 0.001). Frail patients were more likely to have a Mini-Mental State Examination (MMSE) score <24 (55.9% vs. 28.8%, P < 0.001) and take more than five medications (64.1% vs. 47.2%, P = 0.001). Frail patients had a higher incidence of all-cause mortality or readmission (62.8% vs. 47.7%, P = 0.002), all-cause readmission (56.6% vs. 45.9%, P = 0.029), and readmission for non-heart failure (55.2% vs. 41.3%, P = 0.004) during the 3-year follow-up, with a 1.53-fold (95%CI 1.11-2.11, P = 0.009) higher risk of all-cause mortality or readmission, a 1.52-fold (95%CI 1.09-2.11, P = 0.014) higher risk of all-cause readmission, and a 1.70-fold (95%CI 1.21-2.38, P = 0.002) higher risk of readmission for non-clinical heart failure, adjusted for sex, age, polypharmacy, Athens Insomnia Scale, MMSE, LVEF, BADL, and IADL. CONCLUSIONS: Frailty is common in elderly patients with stage B HFpEF. Physical frailty, particularly low physical activity, can independently predict the long-term prognosis in these patients.

Prognostic relevance of left cardiac enlargement in dogs with preclinical myxomatous mitral valve disease.

INTRODUCTION: According to the most recent consensus guidelines on canine myxomatous mitral valve disease (MMVD), dogs with only left atrial enlargement (LAE) or left ventricular enlargement are classified as stage B1. The concomitant presence of LAE and left ventricular enlargement is needed to be classified as stage B2. The primary aim of the study was to evaluate the prognosis in stage B1 and stage B2 according to the revised definition. The secondary aim was to assess the prognostic relevance of LAE in stage B1. ANIMALS: A total of 440 dogs with MMVD, 276 in stage B1 and 164 in stage B2. MATERIALS AND METHODS: Retrospective and observational study. The left atrium-to-aorta ratio and the left ventricular end-diastolic diameter normalized were used to define cardiac dimensions. The long-term outcome was assessed by telephone interviews with owners and referring vets. Both cardiac-related and all-cause mortality were evaluated. RESULTS: Stage B1 dogs had a longer median survival time than stage B2, considering both cardiac-related death (2344 vs. 1341 days; P<0.001) and all-cause mortality (1832 vs. 855 days; P<0.001). Age, left atrium-to-aorta ratio, and the left ventricular end-diastolic diameter normalized were independent predictors of cardiac-related death and all-cause mortality. Among stage B1, dogs with LAE lived shorter than those without LAE (1183 vs. 1882 days; P=0.005) considering all-cause mortality. DISCUSSION AND CONCLUSIONS: Stage B1 dogs lived longer than stage B2 dogs. Among stage B1, LAE had prognostic relevance considering all-cause mortality. This finding could add useful prognostic information in the management of preclinical MMVD.

Left ventricular diastolic abnormalities in vegetarians compared with non-vegetarians.

Vegetarians have less hypertension, diabetes mellitus and obesity, hence possibly lower risk of congestive heart failure (HF). We studied associations between vegetarian diets and echocardiographic markers of stage B HF. In a cross-sectional study, dietary pattern was ascertained by a validated FFQ. Echocardiograms were interpreted using standardised criteria. Participants were free-living subjects in Southern California who were older Adventist Health Study-2 cohort members. After exclusions, 133 subjects aged >60 years were enrolled. Their mean age was 72·7 (sd 8·7) years, 48·1 % were female, 32 % were African American and 71 % were vegetarian. Non-vegetarians had higher body weight (80·3 (sd 15·17) kg v. 71·3 (sd 16·2), P < 0·005), body surface area (1·92 (sd 0·24) m2v. 1·81 (sd 0·22) m2, P = 0·01) and prevalence of hypertension (63 % v. 47 %, P = 0·10). Adjusting for age, sex, race and physical activity, it is found that vegetarians had greater echocardiographic mitral annular e' velocity (a measure of left ventricular (LV) relaxation) 7·44 v. 6·48 (non-vegetarian) cm/s (P = 0·011) and a yet greater contrast when vegans (7·66 cm/s, P = 0·011) were the group of interest. The ratio mid-to-late-diastolic mitral flow velocity (E/A) was also higher in vegans compared with non-vegetarians (1·02 and 0·84, respectively, P = 0·008). Mediation analyses suggested these associations may be partly related to higher blood pressures and BMI in the non-vegetarians. We conclude that vegetarians, especially vegans, appear to have better LV relaxation and fewer diastolic abnormalities than others. As dietary exposure is modifiable, one may speculate pending further investigation about the potential for reduction of stage B HF and later mortality.

Impact of guideline adherence on the prognosis of Barcelona clinic liver cancer stage B hepatocellular carcinoma.

BACKGROUND: Patients with Barcelona clinic liver cancer (BCLC) stage B hepatocellular carcinoma (HCC) are considerably heterogeneous in terms of tumor burden, liver function, and performance status. To improve the poor survival outcomes of these patients, treatment approaches other than transarterial chemoembolization (TACE), which is recommended by HCC guidelines, have been adopted in real-world clinical practice. We hypothesize that this non-adherence to treatment guidelines, particularly with respect to the use of liver resection, improves survival in patients with stage B HCC. AIM: To assess guideline adherence in South Korean patients with stage B HCC and study its impact on survival. METHODS: A retrospective analysis was conducted using data from 2008 to 2016 obtained from the Korea Central Cancer Registry. Patients with stage B HCC were categorized into three treatment groups, guideline-adherent, upward, and downward, based on HCC guidelines recommended by the Asian Pacific Association for the Study of the Liver (APASL), the European Association for the Study of the Liver (EASL), and the American Association for the Study of Liver Diseases (AASLD). The primary outcome was HCC-related deaths; tumor recurrence served as the secondary outcome. Survival among the groups was compared using the Kaplan-Meier method and the log-rank test. Predictors of survival outcomes were identified using multivariable Cox regression analysis. RESULTS: In South Korea, over the study period from 2008 to 2016, a notable trend was observed in adherence to HCC guidelines. Adherence to the EASL guidelines started relatively high, ranging from 77% to 80% between 2008 and 2012, but it gradually declined to 58.8% to 71.6% from 2013 to 2016. Adherence to the AASLD guidelines began at 71.7% to 75.9% from 2008 to 2010, and then it fluctuated between 49.2% and 73.8% from 2011 to 2016. In contrast, adherence to the APASL guidelines remained consistently high, staying within the range of 90.14% to 94.5% throughout the entire study period. Upward treatment, for example with liver resection, liver transplantation, or radiofrequency ablation, significantly improved the survival of patients with BCLC stage B HCC compared to that of patients treated in adherence to the guidelines (for patients analyzed according to the 2000 EASL guidelines, the 5-year survival rates were 63.4% vs 27.2%, P < 0.001), although results varied depending on the guidelines. Progression-free survival rates were also significantly improved upon the use of upward treatments in certain groups. Patients receiving upward treatments were typically < 70 years old, had platelet counts > 105/µL, and serum albumin levels ≥ 3.5 g/dL. CONCLUSION: Adherence to guidelines significantly influences survival in South Korean stage B HCC patients. Curative treatments outperform TACE, but liver resection should be selected with caution due to disease heterogeneity.

Improving the Characterization of Stage A and B Heart Failure by Adding Global Longitudinal Strain.

BACKGROUND: Current guidelines distinguish stage B heart failure (SBHF) (asymptomatic left ventricular [LV] dysfunction) from stage A heart failure (SAHF) (asymptomatic with heart failure [HF] risk factors) on the basis of myocardial infarction, LV remodeling (hypertrophy or reduced ejection fraction [EF]) or valvular disease. However, subclinical HF with preserved EF may not be identified with these criteria. OBJECTIVES: The purpose of this study was to assess the prediction of incident HF with global longitudinal strain (GLS) in patients with SAHF and SBHF. METHODS: The authors analyzed echocardiograms (including GLS) in 447 patients (age 65 ± 11 years; 77% male) enrolled in a prospective study of HF in individuals at risk of incident HF, with normal or mildly impaired EF (≥40%). Long-term follow-up was obtained via data linkage. Analysis was performed using a competing risks model. RESULTS: After a median of 9 years of follow-up, 50 (10%) of the 447 patients had new HF admissions, and 87 (18%) died. In multivariable analysis, all imaging variables were independent predictors of HF admissions, including left ventricular ejection fraction (LVEF) (HR: 0.97 [95% CI: 0.94-0.99]), LV mass index (HR: 1.01 [95% CI: 1.00-1.02]), left atrial volume index (HR: 1.02 [95% CI: 1.00-1.05]), and E/e' (HR: 1.05 [95% CI: 1.01-1.24]), incremental to clinical variables (age and Charlson comorbidity score). However, the addition of GLS provided value incremental to both clinical and other echocardiographic parameters (P = 0.004). Impaired GLS (<18%) (HR: 4.09 [95% CI: 1.87-8.92]) was independent and incremental to all clinical and other echocardiographic variables in predicting HF, and impaired LVEF, left ventricular hypertrophy, left atrial enlargement, high E/e', or SBHF were not predictive. CONCLUSIONS: The inclusion of GLS as a criterion for SBHF would add independent and incremental information to standard markers of SBHF for the prediction of subsequent HF admissions.

Laparoscopic versus open liver resection for resectable HCC with BCLC stage B: a propensity score-matched analysis.

To date, there is little knowledge about the value of laparoscopic liver resection (LLR) for hepatocellular carcinoma (HCC) patients with Barcelona Clinic Liver Cancer (BCLC) stage B. Thus, this study was performed to assess the perioperative and oncological outcomes of LLR for these patients by comparison with open liver resection (OLR). Between April 2015 and October 2018, a total of 217 resectable HCC patients with BCLC stage B were eligible for this study. Patients were divided into the LLR group and the OLR group according to different procedures. Propensity score matching (PSM) was conducted to adjust for known confounders. Short- and long-term outcomes were compared between the two groups. LLR was performed in 75 of the 217 included patients. After PSM, 72 patients with well-balanced baseline levels were enrolled into each group. Although the operative time was significantly longer in the LLR group than in the OLR group (median, 237.5 vs. 210 min, P = 0.024), the intraoperative blood loss was significantly less in the LLR group than in the OLR group (median, 200 vs. 350 ml, P = 0.005). Patients in the LLR group had fewer complications than those in the OLR group (P = 0.035). Furthermore, overall survival (OS, P = 0.827) and recurrence-free survival (RFS, P = 0.694) were comparable between the two groups. LLR for resectable HCC patients with BCLC stage B is safe and feasible in carefully selected patients and has superior perioperative outcomes and similar survival rates compared with OLR.

Asymptomatic Canine Degenerative Valve Disease: Diagnosis and Current and Future Therapies.

Degenerative valve disease (DVD) is the leading cause of heart disease and heart failure in the dog. The first consensus statement published in 2009 by the American College of Veterinary Internal Medicine was updated in 2019 and provides guidelines for the diagnosis and treatment of DVD. These updated guidelines recommend treatment with pimobendan in stage B2 DVD characterized by sufficient left heart enlargement. Asymptomatic dogs with DVD that do not meet or exceed the definition of stage B2 are considered stage B1. No treatment is recommended in stage B1 DVD. This article discusses the relevant scientific background and practical application of the updated DVD guidelines related to stage B. In addition, management of common sequelae of DVD that can result in clinical signs unrelated to congestive heart failure will be reviewed. The impact of new evidence on current recommendations and a glimpse into novel diagnostic approaches and possible future therapies will also be addressed.

Epidemiology of Asymptomatic Pre-heart Failure: a Systematic Review.

PURPOSE OF REVIEW: To quantify the prevalence of asymptomatic pre-heart failure (pre-HF), progression to more severe stages, and associated mortality. RECENT FINDINGS: A systematic review was conducted between 01 January 2010 and 12 March 2020 (PROSPERO: CRD42020176141). Data of interest included prevalence, disease progression, and mortality rates. In total, 1030 sources were identified, of which, 12 reported on pre-HF (using the ACC/AHA definition for stage B HF) and were eligible. Prevalence estimates of pre-HF ranged from 11 to 42.7% (10 sources) with higher estimates found in the elderly, in patients with hypertension, and in men. Three studies reported on disease progression with follow-up ranging from 13 months to 7 years. The incidence of symptomatic HF (HF/advanced HF) ranged from 0.63 to 9.8%, and all-cause mortality from 1.6 to 5.4%. Further research is required to investigate whether early detection and intervention can slow or stop the progression from asymptomatic to symptomatic HF.